Glaucoma is one of the leading causes of irreversible blindness. Although the occurrence of glaucoma is more frequent in the elderly, the disease affects all age groups. Glaucoma is a significant cause of visual impairment and results in significant loss of productivity in affected individuals. Glaucoma is not a single disease process, although it may simply be characterized as a condition where the intraocular pressure (IOP) is too high for the normal functioning of the optic nerve. Damage to the optic nerve is associated with progressive loss of visual field, and if untreated can lead to total irreversible blindness.
As the term glaucoma encompasses several disease states, the causes of glaucoma are many. This invention is directed toward the treatment of one class of glaucoma, primary open angle glaucoma, where there is a normal anterior chamber and an open anterior chamber angle. This disease state may occur spontaneously or may be secondary to treatment for another systemic disease state. An example of the latter is elevated intraocular pressure secondary to corticosteroid treatment for inflammation.
The administration of corticosteroid ocular anti-inflammatory agents has been linked to elevated intraocular pressure in the human eye [Armaly, Arch. Ophth., 70:482 (1963); Becker et al., Arch. Ophthal., 70:500 (1963); Nicholas, Arch. Ophthal., 72:189 (1964); Armaly, Arch. Ophthal., 70:492 (1963)]. Corticosteroid therapy for systemic inflammation may also induce elevated intraocular pressure. These compounds also are commonly administered to relieve ocular inflammation. These effects can be observed when one member of the class of corticosteroids is topically administered to normal and glaucomatous eyes. [Cantrill, et al., Am. J. Ophthal., 79:6:1012 (1975)]. The pressure elevating effect of topically applied corticosteroids has been successfully reproduced in rabbits [Levene,.et al., Am. J. Ophthal., 78:3:509 (1974); Bonomi, et al., Graefes Arch. Ophth., 209:73 (1978); Podos, Symp. on Eye Dis., 81:632 (1976); Knepper, et al., Exp. Eye Res., 27:567 (1978)].
Topical instillation of dexamethasone, (9-alpha-fluoro-16-methyl prednisolone) to the eye results in a condition similar to glaucoma; that is, elevation of intraocular pressure (IOP) in man. This undesirable side effect of corticosteroid treatment, if unchecked, may result in permanent debilitating effects upon the eye. These undesirable effects include visual field loss or other impairment of visual acuity resulting from optic nerve damage. These effects are similar to those seen in idiopathic primary open angle glaucoma. The similarity of corticosteroid induced glaucoma to idiopathic is primary open angle glaucoma coupled with the reproducible effects of corticosteroid dexamethasone induced glaucoma in the rabbit indicate that dexamethasone induced glaucoma is a good model of human primary open angle glaucoma as well as corticosteroid induced glaucoma.